Department of Energy, Environmental and Chemical Engineering, Washington University in St. Louis, St. Louis, USA.
Division of Biological and Biomedical Sciences, and Institute of Materials Science and Engineering, Washington University in St. Louis, St. Louis, USA.
Biotechnol J. 2017 Oct;12(10). doi: 10.1002/biot.201700422. Epub 2017 Sep 25.
As yields for biological chemical production in microorganisms approach their theoretical maximum, metabolic engineering requires new tools, and approaches for improvements beyond what traditional strategies can achieve. Engineering metabolite dynamics and metabolite heterogeneity is necessary to achieve further improvements in product titers, productivities, and yields. Metabolite dynamics, the ensemble change in metabolite concentration over time, arise from the need for microbes to adapt their metabolism in response to the extracellular environment and are important for controlling growth and productivity in industrial fermentations. Metabolite heterogeneity, the cell-to-cell variation in a metabolite concentration in an isoclonal population, has a significant impact on ensemble productivity. Recent advances in single cell analysis enable a more complete understanding of the processes driving metabolite heterogeneity and reveal metabolic engineering targets. The authors present an overview of the mechanistic origins of metabolite dynamics and heterogeneity, why they are important, their potential effects in chemical production processes, and tools and strategies for engineering metabolite dynamics and heterogeneity. The authors emphasize that the ability to control metabolite dynamics and heterogeneity will bring new avenues of engineering to increase productivity of microbial strains.
随着微生物生物化学生产的产量接近理论最大值，代谢工程需要新的工具和方法来实现传统策略无法达到的改进。工程代谢物动力学和代谢物异质性对于进一步提高产品滴度、生产力和产量是必要的。代谢物动力学是指代谢物浓度随时间的总体变化，它源于微生物需要适应细胞外环境来调节其代谢，这对于控制工业发酵中的生长和生产力非常重要。代谢物异质性是指在同克隆群体中代谢物浓度的细胞间变化，它对总体生产力有重大影响。单细胞分析的最新进展使我们能够更全面地了解驱动代谢物异质性的过程，并揭示代谢工程的目标。作者介绍了代谢物动力学和异质性的机械起源概述，为什么它们很重要，它们在化学生产过程中的潜在影响，以及工程代谢物动力学和异质性的工具和策略。作者强调，控制代谢物动力学和异质性的能力将为提高微生物菌株的生产力带来新的工程途径。
